Structure, function, signs, and symptoms

Typically, the history is the most important diagnostic aid in evaluating thyroid disorders, although the physical findings serve to bolster your suspicions. Thyroid size does not reflect thyroid function. First sort out the functional state: hypothyroid, hyperthyroid, or euthyroid (normal function). Then examine the thyroid to see whether it is too big or contains any lumps and to search for associated lymphadenopathy.

Causes of Childhood Hypothyroidism

The most common cause of hypothyroidism in childhood is autoimmune thyroiditis (Hashimoto’s disease, or lymphocytic thyroiditis). Lymphocytic infiltration causes firm diffuse enlargement of the thyroid and a pebbled surface. The anterior pituitary, sensing the lack of thyroid hormone (loss of feedback inhibition), increases the secretion of thyroid-stimulating hormone (TSH), causing the thyroid to enlarge further. Although the gland can grow in response to TSH, it cannot necessarily keep up in terms of thyroxine (T₄) production. Because the autoimmune process is destructive, some patients have a small or undetectable thyroid gland at presentation. A child with hypothyroidism secondary to hypothalamic-pituitary disease does not have thyroid enlargement (a goiter).

Congenital hypothyroidism is usually due to either absence of the thyroid or a hypoplastic thyroid that may be ectopic (located anywhere along the embryologic line of descent from the back of the tongue to the anterior neck.)

Case History 2

History. Shauna, age 15 years, says, “I was the tallest in my class in fifth grade, but I have not grown since then, and my periods haven’t started” (Fig. 16–5).

FIGURE 16–5 A, Shauna with the typical facial features of profound hypothyroidism. Note the puffy face and neck and the coarse, dry hair. B, Shauna after 4 months of treatment with thyroid hormone.

Your physical examination reveals all of the physical findings for hypothyroidism that are listed in Table 16–1. You particularly note the characteristic puffiness around Shauna’s upper face and eyes. In this case, because of profound hypothyroidism, there is also a more generalized swelling, including the neck.

TABLE 16–1 Causes of Precocious Puberty

Type of Precocious Puberty	Underlying Cause
Central	Idiopathic Hypothalamic hamartoma Germinoma (pinealoma) Other cerebral tumors or malformations Severe hypothyroidism Secondary to cranial irradiation
Gonadal	Benign precocious thelarche (? central) Ovarian cysts, benign McCune-Albright syndrome (polyostotic fibrous dysplasia of bone, ovarian cysts, large irregular café-au-lait spots) Leydig cell hyperplasia (familial testotoxicosis) Gonadal tumors (male and female) Isolated premature menses (? central)
Adrenal	Benign premature adrenarche Congenital adrenal hyperplasia Adrenal tumors
Iatrogenic	Exogenous sources

With treatment for hypothyroidism, Shauna’s menses start almost immediately. She grows an inch and loses 4 kg (9 lb) during 4 months of therapy.

In a few infants, hypothyroidism is caused by a congenital enzyme defect in thyroid hormonogenesis. In such instances, a goiter is present. In many countries, congenital hypothyroidism is now detected in the presymptomatic stage, before any significant intellectual deficit occurs, through blood spot screening between the second and fifth days of life. If congenital hypothyroidism is left untreated, the clinical manifestations may not become fully apparent until around the third month of life.

Key Point

Thyroid hormone is essential for adequate development of brain cell function and interneuronal connections. With absence of the hormone over the first few months of life, the infant suffers marked and irreversible developmental delay, the magnitude of the intellectual deficit increasing with each passing week. Universal newborn screening for hypothyroidism is therefore essential.

The infant with untreated congenital hypothyroidism has a low core body temperature, slow pulse rate, prolonged neonatal jaundice (because of poor hepatic conjugation of bilirubin), dry skin and hair, a large posterior fontanel (greater than 0.5 cm), poor head control, poor muscle tone, an enlarged tongue, a characteristically puffy face, and a hoarse cry (Fig. 16–6). The parents may report poor feeding and constipation. If acquired hypothyroidism develops after age 2 or 3 years, no permanent intellectual deficit is thought to occur.

FIGURE 16–6 Typical appearance of congenital hypothyroidism in a 3-month-old baby.

Acquired hypothyroidism must be ruled out in any child with unexplained growth retardation. The child’s appetite is generally diminished, yet there is a modest weight gain, leading to a decrease in height-to-weight ratio. Such children are not massively obese; by contrast, prepubertal obese children generally grow well in height. Constipation is a common feature. In children with type 1 diabetes mel litus, you must always rule out the coexistence of autoimmune thyroid disease, usually lymphocytic thyroiditis, because these disorders are commonly related.

Examining newborns and young infants

In a newborn or young infant, use a different technique to examine the thyroid. Place your hand under the child’s back, between the scapulae, and raise the baby’s shoulders, allowing the head to fall back gently until it rests on the examining table or a parent’s lap. If the thyroid is enlarged, this maneuver will expose it, allowing you to palpate with the second and third fingers of your other hand (Fig. 16–8).

FIGURE 16–8 Palpation of the thyroid gland in an infant.

Examining young children and adolescents

In the young child or adolescent, first observe the gland. Then, after gaining the child’s cooperation, palpate it. We generally examine from the front, as follows. Locate the cricoid cartilage, which is the smaller tracheal cartilage, just below the notched thyroid cartilage or Adam’s apple. Palpate just below the cricoid cartilage for a soft ribbon of tissue that moves with swallowing and is the normal isthmus. With practice you will become expert at finding the thyroid isthmus. Then rest both thumbs gently over the lobes of the thyroid, and ask the child to swallow. While the child swallows, move your thumbs with the child’s skin, up and down over the thyroid to outline its size. Note any nodules or irregularities you feel. You can also examine the thyroid in the traditional way, from behind the child: Place the second and third fingers of your examining hand over the gland to estimate its size, and ask the child to swallow. We often joke with older children who hate to have their necks touched that we have never choked anyone and are not allowed to!

Always measure and record the gland size so that any significant changes between visits are documented. With a measuring tape, measure from upper to lower pole and the greatest vertical dimension of the isthmus. Record the results in diagrammatic form, indicating any nodules or other irregularities.

The normal thyroid weight in grams corresponds approximately to the child’s age in years; a normal adult gland weighs 20 to 25 g and is the size of your thumb from the distal interphalangeal joint to the tip. The thyroid can be palpated in most older children. Because its normal consistency is soft, the contours can barely be seen, and the gland is rather flat when the child hyperextends the neck. Once the thyroid gland becomes firm, as in autoimmune thyroiditis (Hashimoto’s disease), or hard, as in a carcinoma, you should recognize the difference in consistency, even though enlargement may not be striking. Some carcinomas, however, may not be hard to the touch because consistency is not always a reliable diagnostic sign.

Most midline neck masses are thyroid glands or thyroid remnants. A central rounded midline mass between the thyroid and the chin is almost certain to be a thyroglossal duct cyst (Fig. 16–9), derived from a remnant of the thyroglossal duct, which runs from the foramen cecum of the tongue downward to the cricoid cartilage during fetal development. When the child sticks out the tongue, the mass moves upward. The child may present initially with an infected thyroglossal duct cyst. Sometimes, the gland fails entirely to migrate downward from the foramen cecum and manifests clinically as an oval or rounded midline mass at the base of the tongue (Fig. 16–10). This lingual thyroid usually represents all of the thyroid that the child has. Most lingual thyroids are treated with daily therapy using l-thyroxine, which suppresses pituitary thyrotropin (TSH) secretion, causing the lump to shrink markedly.

FIGURE 16–9 Thyroglossal duct cyst, a midline neck mass.

FIGURE 16–10 Thyroid scan in an infant demonstrating uptake of the radionuclide at the base of the tongue in a lingual thyroid (arrow).

The thyroid may be absent, small, ectopic, or enlarged. If both lobes are enlarged fairly symmetrically, it is described as diffusely enlarged. The normal gland may have slight undulations on palpation, but if you find one or more distinct lumps, the child has either a solitary nodule or a multinodular goiter.

A diffusely enlarged, nontender gland that is soft to somewhat firm in consistency is compatible with Graves disease. By contrast, a tender, diffusely swollen gland in a child who withdraws when the gland is touched is likely to represent subacute thyroiditis attributed to a viral cause. Thyroid-stimulating antibodies interact with the TSH receptor on the thyroid cell, producing the constant stimulation of Graves disease. In subacute thyroiditis, disrupted cells produce a sudden thyroid hormone discharge, causing a transient hyperthyroid period, which is often followed by a longer hypothyroid state, then by euthyroidism within 3 to 6 months. A similar sequence is seen in a condition called silent thyroiditis, so called because it is not painful. Silent thyroiditis is most common in the postpartum period but does occur at all ages and in both sexes; it has an autoimmune etiology.

If one or more nodules are found in a child with hyperthyroidism, the cause is probably a benign adenoma, called toxic nodular goiter, which is overproducing thyroid hormone. This condition is seen more commonly in adults. The discrete smooth, oval or round nodules are firmer than the surrounding gland but not rock-hard. When the child swallows, they move up and down and are not fixed to extrathyroidal tissues. Rare TSH-secreting pituitary adenomas can cause diffuse thyroid enlargement and systemic signs of hyperthyroidism but without the eye findings characteristic of autoimmune (Graves) disease.

An eye examination yields important clues for diagnosis and management of thyroid disease. In hyperthyroidism, the palpebral fissures are widened and blinking is diminished, giving the child a staring appearance. In autoimmune Graves disease, the eye muscles can swell to several times their normal size, and the retro-orbital fat pad enlarges, causing the eye to bulge out of the orbit (proptosis), often with injection (prominent small surface vessels) and edema of the bulbar conjunctiva (chemosis). Because individuals with proptosis have difficulty closing their lids, corneal ulceration may occur, causing red, sore eyes, particularly in the morning. Ask the parent whether the child closes the eyes when sleeping. Without adequate tears and with open lids, the cornea becomes dry and vulnerable to ulceration. Enlarged ocular muscles produce an imbalance of extraocular muscle function, sometimes sufficient to cause diplopia, which may be unrecognized by affected patients until they are asked to look upward and outward, the direction of gaze in which diplopia can first be elicited. Usually, there is some loss of convergence, and the child cannot cross the eyes to the usual extent when trying to follow the physician’s finger as it is moved toward the nose.

Thyroid bruits are characteristic of Graves disease, but this sign is not very useful in children. The problem with auscultating the neck in children is that if you press hard enough with the stethoscope, you can make anything whistle.

Infants may be born with neonatal hyperthyroidism from transplacental passage of thyroid-stimulating immunoglobulin, an antibody produced in a mother who has active or treated Graves disease with persistent circulating antibody. Although these babies have the same signs as older children, they are more likely to have hyperthermia and cardiac tachyarrhythmias and to develop congestive heart failure.

Euthyroid states

Someone who has had hyperthyroidism may continue to have a palpably enlarged thyroid gland, even though the disease has disappeared spontaneously or has been treated. Not all patients with autoimmune (Hashimoto’s) thyroiditis become hypothyroid; some remain euthyroid for years and may never develop hypothyroidism.

Ruling out thyroid carcinoma

Children who have single or multiple nodules are usually euthyroid. When a nodule is found, the parents are understandably concerned about cancer. It is not always possible to rule out thyroid cancer on clinical grounds alone, but some characteristics can influence your suspicions. Carcinoma in children may go undetected for many years and is generally asymptomatic; the swelling may be more readily recognized by someone who does not see the child every day. Thyroid carcinoma (usually the papillary type) is typically hard, not merely firm. It may be smooth and oval, but if it has extended beyond its capsule, it may feel irregular. More than one nodule decreases the likelihood of carcinoma but does not exclude it completely. Benign adenomas or simple colloid cysts may also present as single or multiple nodules.

Because external irradiation to the head and neck is associated with an increased incidence of both benign and malignant thyroid lesions, patients who have been exposed to therapeutic irradiation should be examined annually.

Medullary thyroid carcinoma, the best-recognized familial thyroid tumor, has an autosomal dominant pattern of inheritance and often appears in childhood. The tumor originates in the parafollicular or C cells that produce calcitonin. It is essential to screen children with a positive family history of medullary carcinoma for genetic mutations associated with multiple endocrine neoplasia syndrome, type 2 (MEN2). Such children often require prophylactic thyroidectomy by age 5 years.

Hypercalcemic states

Hypercalcemia causes constipation, polyuria, and thirst. Other complaints are mood changes and epigastric distress. Belly pain in an infant usually manifests as vomiting, and mood changes manifest as fussiness and crying.

Hypocalcemic states

Maternal hyperparathyroidism can result in transient symptomatic low serum calcium levels in the newborn, a fact that emphasizes the need to take a good history of the mother’s health for every baby you examine.

The endocrine basis of signs and symptoms

Cortisol and aldosterone are essential for survival, whereas adrenal androgens are responsible for initiating the growth of pubic and axillary hair and the oiliness of skin and hair and for changing the child’s body build in the immediate preadolescent years (the physiologic anabolic steroid effect). Subsequently, the testes and, to a lesser extent, the ovaries play an essential role in completing this process of adrenarche. Endocrinologists are probably the only physicians who care about the presence of pubic and axillary hair, but we recommend that you also take an interest.

Overproduction of adrenal cortical hormones may dramatically change a child’s appearance. Antenatal exposure of a female fetus to excess androgens causes sexual ambiguity; postnatal exposure results in partial sexual precocity in males and virilization in females. Aldosterone excess causes hypertension, a rare primary adrenal abnormality in childhood; cortisol excess produces Cushing syndrome.

Pheochromocytoma, a tumor of the adrenal medulla or extra-adrenal chromaffin neural crest tissue, causes sustained or paroxysmal hypertension because of excessive secretion of catecholamines (epinephrine and norepinephrine). Headaches and spells with pallor and sweating are among the cardinal symptoms.

Evaluating cushing syndrome

The overwhelming majority of obese children do not have Cushing syndrome, but the few who do may be difficult to identify. Cushing syndrome most commonly occurs as a result of exogenous administration of glucocorticoids. Whether cortisol excess is of exogenous or endogenous origin, the degree of excess determines the severity of the clinical features. Most prepubertal obese children are tall for their ages and have a significant family history of obesity, but the child with Cushing syndrome often displays a recent weight gain, poor statural growth, and fatigue, weakness, or mood changes.

Observe the child from all sides to assess body fat distribution. In adults with Cushing syndrome, the adiposity is clearly central; they have slim limbs, thin hands, and a rounded face. Young children with Cushing syndrome have more generally distributed body fat that is still maximal in the face, trunk, and cervical region, but the adiposity is chunkier and more solid in the very young, almost seeming to bury their small features (Fig. 16–13). We never tell patients that they have a buffalo hump, preferring the term increased posterior cervical fat pad because it sounds less derogatory.

FIGURE 16–13 Clinical features of Cushing syndrome in a 4-year-old boy.

Striae (stretch marks) are unusual before the teen years. In Cushing syndrome, these marks are violaceous rather than the pink to silver color seen in obesity or during rapid growth in normal adolescents. Check the scalp hairline. Fine lanugo hair growing down from the scalp to the forehead, from the occipital region to the nape of the neck, and sweeping down the lateral cheek suggests excess cortisol exposure. A small amount of fine hair may be distributed over the entire body, including the pubic region. Cortisol excess increases red cell production, giving the child a ruddy, plethoric complexion. It also inhibits protein synthesis, resulting in muscle atrophy, decreased strength, thin fragile skin and vasculature, and susceptibility to bruising. Osteoporosis, a significant sequela, may be manifested by back pain due to vertebral compression fractures. This condition is particularly evident in children who have received high-dose glucocorticoid therapy for prolonged periods to control a primary disease (see Fig. 16–14).

FIGURE 16–14 A, Spinal radiograph of a 10-year-old boy with Duchenne muscular dystrophy who experienced severe osteoporosis after receiving high doses of glucocorticoid for 3 years to improve muscle function. Note the marked wedging of the anterior vertebral bodies, which caused the patient so much pain that he was unable to continue to crawl and was no longer able to assist with transfers from bed to wheelchair. B, After treatment for 2 years, the vertebral bodies show improved density. The patient’s pain disappeared, and his mobility was restored to the previous level.

When the glucocorticoid and adrenal androgen are in excess, secondary sexual hair may appear in an otherwise prepubertal child. In a boy, this finding is not accompanied by an increase in testicular size because the androgen is adrenal rather than testicular in origin.

Cortisol enhances norepinephrine’s action on the vasculature and has some intrinsic mineralocorticoid effect, increasing sodium retention; therefore, the blood pressure may be elevated or at the upper limit of normal.

Once you suspect Cushing syndrome, how can you localize its cause? Increased pigmentation suggests a pituitary etiology, such as an adenoma with increased adrenocorticotropic hormone (ACTH) secretion, although the pigmentary change is far less dramatic than in Addison disease. Always note the parents’ complexion so as not to be misled by familial pigmentary characteristics. Pituitary tumors can press on the optic chiasm, causing visual field defects—classically, bitemporal hemianopsia with optic atrophy (see Chapter 8). On clinical grounds alone, it can be extremely difficult to differentiate Cushing syndrome with a central etiology from that caused by an adrenal tumor. Sophisticated laboratory and imaging investigations are usually required to make the distinction.

Androgen excess

General definitions

The occurrence of pubertal changes before age 8 years in girls or 9 years in boys and the delay of pubertal changes beyond age 13 years in girls or 14 years in boys should be evaluated. However, evidence exists to suggest that close to 10% of white American girls have Tanner 2 breast development before their eighth birthday and that this rate is higher in black American girls. Puberty depends on the secretion of gonadotropin-releasing hormone (GnRH) through increased activity of the GnRH pulse generator.

Central precocious puberty is idiopathic in the majority of cases. Identifiable causes include hypothalamic tumors and hamartomas (normal tissue in a tumorous collection). Noncentral precocious puberty does not originate in the hypothalamic-pituitary axis; it results from increased sex hormone secretion from the adrenal glands or gonads. CAH is one example. See Table 16–1 for a list of the causes of precocious puberty.

Obtaining the history

Although establishing when secondary sexual changes began is helpful in a child with precocious puberty, the reported sequence may be approximate because of the gradual nature of puberty. An exception is the time of the first menstrual period, which most girls remember. Vaginal bleeding may occasionally be a first sign of puberty; remember the possibility of sexual abuse or self-insertion of foreign objects.

For a child whose pubertal development is abnormal, you must evaluate the psychosocial impact. Is excessive masturbation a problem? How do the parents deal with the problem? Do they hug and cuddle this 4-year-old who looks and sounds like a small man but acts like a small child (Fig. 16–25)?

FIGURE 16–25 Precocious puberty in a 4-year-old boy as a result of Leydig cell hyperplasia (activation of the LH [luteinizing hormone] receptor). Note the increased size of the phallus, maturity of the scrotum, and muscular body habitus.

A family history of similar delay can reassure the teenager, often a boy, who shows slow pubertal maturation. Excessive physical activity—gymnastics, ballet, or running—can delay secondary sexual development and menarche. Similarly, eating disorders inhibit sexual maturation and may cause primary or secondary amenorrhea.

Cerebral insults, such as birth asphyxia, hydrocephalus, and cranial irradiation, can be associated with premature or delayed puberty. Because the hypothalamus, pituitary, and optic chiasm are in close anatomic proximity, expanding masses may produce a combination of decreased vision, GHD, and either precocious or delayed puberty.

Approach to physical examination of children with precocious puberty

Take height measurements 6 months to 1 year apart so that you can calculate the child’s growth velocity (see Chapter 3), which is accelerated. Chronic or acute increases in intracranial pressure, secondary to a central tumor, cause optic atrophy or papilledema. Carefully document the visual acuity, visual fields, and extraocular movements. Occasionally, children with hypothyroidism experience precocious puberty, but they are short, with decreased growth velocity for age. Look for café au lait spots, brown macular pigmented areas on the skin with either a smooth border, consistent with neurofibromatosis, or an irregular outline, consistent with McCune-Albright syndrome (Fig. 16–26). Both conditions can be associated with precocious puberty, the former with central precocious puberty. In McCune-Albright syndrome, the precocious puberty is not central, and the child may have multiple ovarian cysts and completely suppressed pituitary gonadotropins, but menses often begin before age 4 years. These children also have the bone lesions of polyostotic fibrous dysplasia, evident on radiographs.

FIGURE 16–26 Precocious puberty in a 3-year-old girl with McCune-Albright syndrome. Note how mature the breasts and nipples appear. A large café au lait spot covers most of the right breast.

Acne is an early pubescent sign, and oily hair and adult-type body sweat odor are manifestations of both adrenal and gonadal activity. Tell the parents that it is appropriate for the child to use deodorant and to shave the axillary hair to avoid teasing.

To examine a child’s breasts, observe the contour, palpate for breast tissue to distinguish true breast tissue from excess adiposity and record the breast diameter. Is the nipple pale, thin, and translucent (Fig. 16–27), as in isolated breast enlargement (precocious thelarche)? This common reversible condition seen in toddlers does not usually progress to true precocious puberty. Alternatively, is the areola dark, indicating high circulating estrogen levels, with a prominent nipple mound, as seen in the 3-year-old girl with McCune-Albright syndrome shown in Figure 16–26? This child demonstrated precocious puberty with menses at age 18 months. Note also the irregular contours of the café au lait spot over the right breast—a clue to the etiology of the precocity.

FIGURE 16–27 Precocious thelarche. Note the immature appearance of the nipples in this self-limited breast enlargement of toddlers.

When there is a significant postnatal increase in circulating estrogen, regardless of its source, the labia minora become enlarged and thickened (Fig. 16–28), vaginal secretions (leukorrhea and/or menses) begin, and breast buds appear.

FIGURE 16–28 Appearance of the external genitalia in a 4-year-old girl with central precocious puberty. The enlarged labia minora are indicated by the arrow. Compare with the normal prepubertal appearance shown in Figure 16–15.

Male breast enlargement, known as gynecomastia, is caused by a temporary increase in the estrogen-to-testosterone ratio. This is usually a benign, spontaneously regressing manifestation of puberty, occurring in most teenage boys. In obese boys, excess adipose tissue can either augment, or mimic adolescent gynecomastia, and is referred to as pseudogynecomastia. It can be very distressing to an adolescent, especially if pronounced. In rare instances, the enlargement can be so extreme and psychologically distressing as to require surgery.

Testicular examination

In boys, the main differentiating feature between adrenal and central (hypothalamic) causes of sexual precocity is that when the testosterone is adrenal in origin, the testicles remain small.

Estimate testicular volume using an orchidometer (Fig. 16–29). A volume of 4 mL is equivalent to 2.5 cm long and corresponds with Tanner stage 2 or the beginning of puberty (see Fig. 3–9). Enlargement suggests a testicular origin for androgen production. If you have a tape measure only, you can derive the testicular volume from measurements of width and length, using the following formula:

FIGURE 16–29 An orchidometer. Note the numerical volumes in milliliters printed on the beads. Prepubertal testicles are 1 to 3 mL.

At Tanner stage 3, testicular volume is between 10 and 12 mL.

Physical findings in delayed puberty

Although by far the most common cause of delayed puberty is physiologic (constitutional) delay, usually associated with delayed growth, the history and physical examination helps exclude pathologic causes. A classification dividing the causes into central (hypothalamic and/or pituitary) and gonadal is given in Table 16–2. Although the list is not exhaustive, it provides an orderly approach to the evaluation of teenagers who are worried about their sexual development. Their stature may be normal or shorter than normal, and their growth velocity is below normal for their chronologic age. The exceptions are boys with Klinefelter syndrome (karyotype XXY gonadal dysgenesis), who are tall with disproportionately long arms and legs, normal adrenarche, and small testes, which may be cryptorchid. These children are often overweight and may show delayed social and intellectual development.

TABLE 16–2 Causes of Delayed Puberty

In girls, the most common causes of pubertal delay are physiologic (familial or constitutional), poor food intake (as in anorexia nervosa), intensive competitive physical training (as in ballet or gymnastics), and chronic illness.

When pubertal delay is combined with short stature in girls, always consider Turner syndrome (karyotype XO), the physical characteristics of which include a short, wide-based neck, low anterior and posterior hairline, shield-shaped chest, absence of breast development, increased elbow-carrying angle, a short fourth metacarpal (see Fig. 16–12), and spoon-shaped nails with lateral margins buried deeply in the pericuticular skin. In some girls, the signs of Turner syndrome are very subtle, especially if the karyotype demonstrates mosaicism, and the presence of breast development does not preclude the diagnosis. Children with Turner syndrome undergo normal adrenarche, so pubic hair and axillary hair are expected at the appropriate age.

In girls with otherwise normal sexual maturation but delayed onset of menarche or secondary amenorrhea, galactorrhea suggests prolactinoma. Although such a tumor is more common in adults, it may begin in adolescence. Boys with prolactinomas can have similar failure of pubertal progression.

The inability to smell (anosmia) or an impaired sense of smell (hyposmia) may accompany hypothalamic hypogonadism, an association that can be explained because the neurons producing LHRH share their origin with the olfactory nerve. Test the sense of smell (see Chapter 13) in any child with small (and often undescended) testicles and a small penis (less than 2.5 or 3 cm in length and circumference). Remember that it is the intrauterine fetal testosterone level that is responsible for the development of the normal penis size at birth.

Type 2 diabetes mellitus

Strong predictors of type 2 diabetes mellitus (DM) in overweight children are first- or second-degree relatives with diabetes and the presence of acanthosis nigricans (see Fig. 16–23). Not all children who are obese are destined to develop diabetes. The increase in rate of type 2 DM in young people is related to rising rates of obesity in the general population. Obesity in a child older than 6 years, especially when accompanied by parental obesity, correlates with adult obesity, a risk factor for type 2 DM, and also an independent risk factor for adult cardiovascular disease. Careful documentation of the family history should alert you to a genetic predisposition to obesity and provide a stimulus for preventive counseling. Because of concerns about self-esteem, calling attention to personal characteristics of an individual is frowned upon. We often ask parents whether they have any concerns about the child’s growth or weight. Gently questioning the child about lifestyle habits may elicit associated poor eating and exercise habits and excessive sedentary activities. Ask about what activities the child participates in each week, including walking. However, to get a full picture of the situation, it is essential to ask about screen time (TV, computer and video games), which can often be many hours per day. Ask whether the child has a TV, computer, or other electronic gadgets in his or her bedroom. Individual counseling, focused on setting small goals to move toward healthier behaviors, is important. However, population-based remedies are also needed to promote change on a large scale.

The presentation of type 2 DM is generally insidious, with few symptoms at first, much as in adults. With time, polyuria and polydipsia develop once the blood glucose level is sufficiently high. Many children have ketonuria, and diabetic ketoacidosis does occur. With improved public and health professional awareness, children with type 1 DM progress less frequently to ketoacidosis than in the past. However, most are ketotic (have acetone breath and ketones in the urine) and thin. Children with type 2 DM are overweight, but as our population becomes progressively more obese, we are seeing more overweight children, even among patients with onset of type 1 DM, making this unreliable as a differentiating feature. In certain racial groups such as black Americans or among indigenous peoples, it is more likely that the diagnosis will be type 2 DM rather than type 1 DM, but not invariably so. Similarly, in white teens, type 1 DM is most common, but type 2 DM is increasing in this population as well. Type 2 diabetes is rare, but not unknown, before the onset of puberty. The presence of acanthosis nigricans strongly points to type 2 DM as the cause of the diabetes (see Fig. 16–23).

Acute presentation of type 1 diabetes mellitus or acute decompensation in a child previously diagnosed

The diagnosis of diabetes mellitus is generally based on a history of polyuria, polydipsia, and recent weight loss. A high percentage of children with new onset diabetes who later present with diabetic ketoacidosis, have seen a physician for various complaints such as a sore throat, urinary symptoms, or abdominal pain in the days to weeks leading up to their presentation. It is important to be alert to polyuria and polydipsia and screen for diabetes in the clinic with a urinalysis or glucose meter check. Symptoms such as abdominal pain and vomiting suggesting a flulike illness are quite common, especially as the metabolic state deteriorates. An accumulation of ketone bodies (β-hydroxybutyrate and acetoacetate), which results from insulin deficiency and glucagon excess, causes ketoacidosis. The likelihood that a child will present with acute decompensated diabetic ketoacidosis is higher both in children younger than age 5 years and in children and adolescents with previously diagnosed type 1 DM in whom poor adherence to recommended treatment schedules (such as insulin omission), severe intercurrent illness, or both, are superimposed. Although obtunded, they usually recognize person, place, and time and are seldom truly comatose. The history is typically short, a few days to several weeks, with a progressive increase in severity of the symptoms. There may be a family history of diabetes, thyroid disease, or both, but most often no one in the family has type 1 diabetes.

The physical signs reflect acidosis, ketosis, and dehydration. Respiratory compensation for the acidosis results in characteristic rapid but deep sighing (Kussmaul) respirations. The breath has the sweet odor of acetone; it smells like nail polish remover. Look for signs of dehydration, such as dry mucous membranes, lack of tears, decreased tissue turgor (tested by picking up a pinch of anterior abdominal wall skin, then releasing it to see whether it springs back quickly or remains tented), and low blood pressure. Low circulating volume in states of dehydration may be best appreciated from the rapidity of the heart rate rather than the measurement of the blood pressure, which may be low only when measured in the upright position, a dangerous maneuver in the patient with acute presentation or decompensation of diabetes.

A high blood glucose level, estimated at the bedside, usually eliminates other conditions from the differential diagnosis. In relatively rare instances, transient stress hyperglycemia and glycosuria can develop in association with severe infections or in acute asthma treated with β-agonists. Affected individuals do not appear to be susceptible to the development of diabetes at a later date. Refer to standard pediatric texts for a full discussion of childhood diabetes.

Table 16–3 contains a useful checklist for significant issues in the history and physical examination of the child with known diabetes who returns for assessment of diabetes control (Figs. 16–30 and 16–31). It is important to remember that diabetes routines are very demanding for the child or teen and their family and often are not fully observed. Clinicians must remember that lecturing a teen about the potential long-term consequences of diabetes is rarely motivating. Using principles of chronic disease management, acknowledge what is done well and help the child or teen and parents to set concrete goals to work together toward getting better results.

TABLE 16–3 Checklist of Significant Issues in History and Physical Examination for Assessment of Diabetes Control

FIGURE 16–30 Lipohypertrophy in a teenager with type 1 diabetes mellitus who administered most insulin injections into a favorite spot. A, Lower abdomen. B, Upper arm.

FIGURE 16–31 Necrobiosis lipoidica diabeticorum, a skin condition associated with diabetes, is found most commonly on the shins.